The present invention relates to a novel process for preparing 5-(4-hydroxyphenyl)hydantoin, and more particularly to a process for easily preparing 5-(4-hydroxyphenyl)hydantoin of high purity in good yields by reacting glyoxylic acid, urea and phenol in the presence of an acid.
5-(4-Hydroxyphenyl)hydantoin is an important intermediate of D-4-hydroxyphenylglycine which is employed for preparing semi-synthetic penicillins and semi-synthetic cephalosporins.
D-4-hydroxyphenylglycine has been generally prepared by chemically subjecting DL-4-hydroxyphenylglycine to optical resolution. However, such a process has the disadvantage that DL-4-hydroxyphenylglycine must be converted to derivatives such as esterification and acylation products prior to subjecting to optical resolution, or that expensive resolving reagents are required, and also the complication of process steps is unavoidable for racemizing the residual useless L-form.
Yamada et al found that DL-5-(4-hydroxyphenyl)hydantoin can be almost quantitatively converted into D-N-carbamoyl-(4-hydroxyphenyl)glycine by causing cells or treated cells of specific microorganisms at act on the hydantoin in an aqueous medium at pH 7 to 10, as disclosed in U.S. Patent Application Ser. No. 764,635 now U.S. Pat. No. 3,094,741. D-N-carbamoyl(4-hydroxyphenyl)glycine can be converted into D-4-hydroxyphenylglycine in high yields, for instance, by reacting it with an equimolar amount of nitrous acid in the presence of a strong acid. The preparation of D-4-hydroxyphenylglycine according to such a process has no disadvantage incidental to the above-mentioned chemical method of optical resolution, and is technically and economically advantageous. Thus, DL-5-(4-hydroxyphenyl)hydantoin is an important intermediate of D-4-hydroxyphenylglycine.
Hitherto, it is known that 5-(4-hydroxyphenyl)hydantoin is synthesized by the reaction of 4-hydroxybenzaldehyde, ammonium bicarbonate and sodium cyanide according to the Bucherer-Berg's method. However, this method requires the use of dangerous sodium cyanide, and further the obtained crude hydantoin may contain large quantities of by-products caused by the oxidative side reaction of the phenol nucleus under an alkaline condition or may be colored.